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Dual Transcranial Direct Current Stimulation Modulates Hierarchical Functional Network Organization in Post-Stroke Cognitive Impairment: A Randomized Controlled Trial.

Yao Wang·Wan Liu·Wenjie Yang·Jun Hu·Xinxin Cheng·Hao Yu·Yin Shi·Li Liu·Jiang Rao·Guangxu Xu
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Abstract

OBJECTIVE: To evaluate the clinical efficacy of dual transcranial direct current stimulation (tDCS) in patients with post-stroke cognitive impairment (PSCI) and to explore the effects on the hierarchical organization of functional brain networks, ranging from regional synchronization to inter-regional connectivity and global network topology. METHODS: In this randomized, double-blind, sham-controlled trial, 74 PSCI patients received conventional therapy alongside either active dual-tDCS (n&#x2009;=&#x2009;38) or sham stimulation (n&#x2009;=&#x2009;36). Active tDCS targeted the dorsolateral prefrontal cortex (DLPFC) via anodal-left/cathodal-right nodes (2.0&#x2009;mA, 20&#x2009;min/day, 20 sessions). The primary outcome was the Montreal Cognitive Assessment (MoCA). Secondary outcomes included the Mini-Mental Status Examination (MMSE), Stroop Test (ST), Trail Making Test (TMT), Wechsler Memory Scale (WMS), and Barthel Index (BI). A subgroup of 36 participants (18 per group) underwent resting-state functional magnetic resonance imaging (rs-fMRI) to analyze regional homogeneity (ReHo), functional connectivity (FC), and network topology. Partial correlations assessed the association between neuroimaging alterations and clinical improvements. RESULTS: The tDCS group showed significantly greater improvements in MoCA scores (tDCS: 5.74&#x2009;&#xb1;&#x2009;2.76 vs. sham: 2.69&#x2009;&#xb1;&#x2009;2.69; t&#x2009;=&#x2009;4.799, p&#x2009;<&#x2009;0.001) as well as in attention and memory domains compared to the sham group. The rs-fMRI changes included increased ReHo in the right middle temporal gyrus (MTG) and the left inferior frontal gyrus (IFG), and reduced FC between the right MTG-left superior frontal gyrus and left IFG-cerebellum (p&#x2009;<&#x2009;0.05, FWE-corrected). Additionally, small-worldness and global efficiency increased (p&#x2009;<&#x2009;0.05) with these alterations correlating with clinical recovery. Adverse events were rare and self-limiting. CONCLUSION: Dual-tDCS over bilateral DLPFC safely improves cognitive recovery in PSCI. These clinical gains are associated with rs-fMRI alterations, specifically in regional synchronization, inter-regional connectivity, and global topology, which suggest a potential biomarker for monitoring tDCS efficacy, offering a rationale for precision neuromodulation in stroke rehabilitation.

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HumansTranscranial Direct Current StimulationFemaleStrokeMaleDouble-Blind MethodAgedMagnetic Resonance ImagingMiddle AgedCognitive DysfunctionNeuropsychological TestsTreatment OutcomeCognitive Enhancementcognitive impairmentfunctional magnetic resonance imagingstroketranscranial direct current stimulationJournal ArticleRandomized Controlled Trial

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Yao Wang, Wan Liu, Wenjie Yang, Jun Hu, Xinxin Cheng, Hao Yu, Yin Shi, Li Liu, Jiang Rao, Guangxu Xu. 2026. Dual Transcranial Direct Current Stimulation Modulates Hierarchical Functional Network Organization in Post-Stroke Cognitive Impairment: A Randomized Controlled Trial.. https://doi.org/10.1002/cns.71111

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